About 100,000 babies are born each year with severe thalassemia type blood disorders or sickle cell anemia, leading to a lifelong regime of blood transfusions. However, the body cannot efficiently remove iron hence the extra iron in the transfused blood accumulates. This causes a toxic build up in the blood, saturation of the iron storage proteins in the liver and spleen leading to iron-induced liver disease, endocrine disorders and cardiomyopathy. If left untreated, iron induced cardiomyopathy inevitably leads to death, before the child reaches adulthood. Transfusional iron overload can be treated by chelation. Approved iron chelators suffer from severe drawbacks that we aim to overcome with a targeted chelator delivery strategy. We have devised a novel, stable nanoliposome (LDFO) formulation containing a high concentration of the iron chelator desferroxamine (DFO). We will test the hypothesis that the subcutaneous (SC) administration of the novel LDFO results in a therapeutic DFO concentration in the liver and spleen and a sustained level of DFO in the blood. Three specific aims will be completed: In aim 1, we will optimize the Liposomal-DFO formulation. In aim 2, we will establish the Storage Stability of the Liposomal DFO Formulations. In aim 3 we will determine the liposomal DFO pharmacokinetics and biodistribution profile when administered by I.V. and subcutaneous routes. This targeted delivery of DFO to the main iron storage sites in the body will more effectively remove iron from deep tissue sites than infusion of non-encapsulated DFO, will infuse 1/8th of the currently used DFO dose in 1/40th of the current infusion time. The formulation will be easier and safer to administer than Desferal(R). If LDFO is validated, it would be a significant advance for the clinical treatment of transfusional iron overload in pediatric patients.